The Psychopharmacology/Biochemistry Laboratory (PBL) Core directed by Dr. Young, will comprise a research biochemist and a technician. It will utilize existing facilities for high performance liquid chromatography (HPLC) and radioimmunoassay (RIA). The PBL Core will serve as a resource for other investigators, providing drug assays and catecholamine neurotransmitter measures, developing additional assay procedures, and serving a consultative role. The PBL will offer training in HPLC, RIA and other laboratory techniques for research fellows and other staff. The PBL will also conduct a research program focused on pharmacologic in geriatric major depression and mania. The PBL research program represents an extension of ongoing studies of nortriptyline (NT) in major depression and of geriatric mania. The goals are to improve guidelines for clinical and research use of NT and lithium (Li) salts by examining concentration-effect relationships and to examine changes in catecholamine neurotransmitter measures during treatment. Differences in patients with cognitive impairment or abnormal brain morphology are evaluated. The first of two pilot studies proposed will examine relationships between plasma NT and 10-hydroxynortriptyline (10-OH- NT) concentrations and therapeutic response and changes in noradrenergic function in geriatric major depressives, with and without cognitive impairment, treated with fixed dose. Differences in patients with large ventricle-brain ration are also tested. The second pilot study will examine therapeutic response to conventional vs. low plasma Li in geriatric manic patients with and without cognitive impairment. Efficacy and change in noradrenergic and dopaminergic measures will be compared in the two treatment groups; differences in patients with cognitive impairment will be examined.